Arisaph Pharmaceuticals Reports On Promising Results Presented At American Heart Association: Novel Apo A-I Mimetic Peptide Significantly Inhibits Atherosclerosis In Preclinical Animal Study

BOSTON, Nov. 14 /PRNewswire/ -- Arisaph Pharmaceuticals, previously known as Triad Pharmaceuticals, Inc., today commented on the results of a study presented at the 2005 Scientific Sessions of American Heart Association (AHA) meeting in Dallas, Texas. The results, presented by Dr. Moti Kashyap of VA Healthcare System and University California at Irvine, showed that reverse D- 4F (rev D-4F), an apo A-I mimetic peptide designed and synthesized by Arisaph, significantly reduced atherosclerotic lesion area compared with the L-4F mimetic peptide and placebo control in an atherosclerotic animal model and demonstrated potent anti-inflammatory properties, in vitro. Additionally, rev D-4F demonstrated a trend toward superiority compared with the D-4F mimetic peptide in reducing atherosclerotic lesion area. The results of the study show that reverse D-4F is a promising drug candidate for the treatment for atherosclerosis and coronary heart disease, a disease that afflicts more than 14 million people in the United States. In addition to reverse D-4F, Arisaph is applying its proprietary drug discovery platforms to develop other cardiovascular therapies through its partnership with Kos Pharmaceuticals, Inc. and to develop innovative compounds for the treatment of diabetes and cancer.

Apo A-I mimetic peptides are smaller versions of apolipoprotein A-I, the main protein component of HDL or "good" cholesterol, which helps remove dangerous plaque from arteries. Apo A-I and apo A-I mimetic peptides are under investigation as therapies for atherosclerosis because they have been shown to improve the functionality of HDL cholesterol and have significant anti-inflammatory benefits. In designing and synthesizing rev D-4F, Arisaph innovatively utilized retro-inversal chiral chemistry to produce an orally active peptide that exists in a more optimal configuration than the L-4F mimetic peptide, possibly enhancing key structure activity relationships.

The study evaluated the effects of three mimetic peptides, reverse D-4F, D-4F, L-4F, as well as placebo on atherosclerosis in apolipoprotein E-knock- out mice, a well established animal model simulating human atherosclerosis. Following 6 weeks of treatment, measurements of the atherosclerotic lesion showed that both reverse D-4F and D-4F significantly decreased lesion area by 46% and 33%, respectively compared with placebo. Animals treated with reverse D-4F showed the greatest reduction in lesion area, although the difference compared with D-4F was not statistically significant. The animals receiving L-4F showed no difference in lesion size compared with placebo. Additionally, reverse D-4F showed potent anti-inflammatory properties, in vitro, by significantly inhibiting LDL oxidation by endothelial cells, monocyte chemotactic protein-1 expression, and monocyte chemotaxis, important inflammatory events that are involved in atherosclerosis.

"The results of this preclinical study demonstrate that we have created a viable drug candidate with an efficacy profile that is competitive with other atherosclerotic treatments currently being investigated by major pharmaceutical companies," said Christopher P. Kiritsy, President and Chief Executive Officer, Arisaph Pharmaceuticals. "In designing and synthesizing reverse D-4F, we combined our knowledge of the active site of the apo A-I mimetic peptide with the utilization of medicinal chemistry techniques to produce an innovative compound with improved structure activity configuration." Mr. Kiritsy further commented, "By leveraging similar rational drug design techniques, we have made significant progress in creating lead candidates for two other cardiovascular therapies, which would operate by increasing HDL cholesterol."

Reverse D-4F was designed and discovered by Arisaph through sponsored research collaboration with Kos Pharmaceuticals, Inc. . The sponsored research collaboration seeks to develop novel compounds that raise HDL cholesterol or improve the functionality of HDL cholesterol, such as reverse D-4F. In addition to the rev D-4F lead candidate already produced, Arisaph has generated promising drug candidates that are lipase inhibitors and specific niacin analogs, both of which would raise HDL cholesterol. Under the terms of the sponsored research agreement, Arisaph receives funding from Kos to support the research and will receive royalties on sales of certain products that would be developed and marketed by Kos.

About Arisaph

Arisaph, located in Boston, Massachusetts, is an emerging drug discovery and design biopharmaceutical company with active development programs to develop differentiated therapies for diabetes, cancer and cardiovascular disease. Arisaph utilizes proprietary drug discovery platforms to develop "ultra-smart" drugs that are efficacious and act on select targets. Arisaph has successfully applied its specificity profiling and retro-inversal chiral chemistry technology platforms to synthesize promising candidate drugs for six different targets, including lead candidates for DPP IV inhibition to treat type II diabetes and for reverse D-4F, an orally active apo A-I mimetic peptide for treatment of atherosclerosis. Through a license agreement with Tufts University, the Company has exclusive worldwide rights to several important issued patents in the diabetes area and to all intellectual property generated by the Company.

Certain statements in this press release, including statements regarding the Company's research and development efforts, the Company's ability to successfully capitalize on the early stage research, the expected benefits to Arisaph of the Kos relationship, the Company's expectations regarding revenues and cash flows, are forward-looking and are subject to risks and uncertainties. These risks and uncertainties include Kos' and Arisaph's ability to complete the development and obtain regulatory approval for their compounds and products, the market acceptance of the Company's and Kos' products, the growth in sales of these products, the Company's ability to continue to develop new products, the validity, scope and enforceability of the patents of the Company and its licensors covering the Company's compounds and product, the Company's ability to obtain patent protection for new compounds and products developed, the effect of conditions and competitive products in the pharmaceutical industry and the economy in general, as well as certain other risks and uncertainties. Actual results may differ materially from those suggested by forward-looking statements.

Contact: Arisaph Pharmaceuticals Christopher Kiritsy President and CEO (617) 292-3322

CONTACT: Christopher Kiritsy, President and CEO of ArisaphPharmaceuticals, +1-617-292-3322

Web site: http://www.arisaph.com//